Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, South Korea.
Bioorg Med Chem. 2011 Mar 15;19(6):1915-23. doi: 10.1016/j.bmc.2011.01.067. Epub 2011 Feb 3.
The synthesis of a novel series of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives 6a-o, 7a-s and their antiproliferative activities against A375P melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido)-2-methylbenzamide 7c exhibited potent activities (GI(50)=0.27 μM). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf inhibitor (IC(50)=0.26 μM, IC(50)=0.11 μM, respectively), showing a possibility as melanoma therapeutics.
描述了一系列新型 N-(5-氨基-1-(4-甲氧基苄基)-1H-吡唑-4-基)酰胺衍生物 6a-o、7a-s 的合成及其对 A375P 黑色素瘤细胞系的抗增殖活性。大多数化合物对索拉非尼（参比标准）表现出竞争性抗增殖活性。其中，N-(5-氨基-1-(4-甲氧基苄基)-1H-吡唑-4-基)-5-(3-(4-氯-3-(三氟甲基)苯基)脲基)-2-甲基苯甲酰胺 7c 表现出很强的活性（GI(50)=0.27 μM）。特别是，7c 被发现是一种有效的、选择性的 B-Raf V600E 和 C-Raf 抑制剂（IC(50)=0.26 μM、IC(50)=0.11 μM），有可能作为黑色素瘤治疗药物。
